This research program seeks to explain the neurogenesis of respiratory pattern in mammals in terms of the biophysical, synaptic, and network properties of neurons in the central nervous system (CNS). During the award period, research will be conducted to further develop and exploit a novel system for the study of these aspects of respiratory pattern generation. This system consists of the mammalian brainstem and spinal cord in vitro and has unique properties that facilitate experimental analysis of neural mechanisms. Unlike conventional experimental approaches in vivo, the in vitro system allows routine application of most relevant neurobiological techniques to study neural pattern generation, including direct utilization of pharmacological and membrane channel probes in the CNS, and intracellular recording to determine neuronal properties. Information to be obtained from these studies is fundamental for defining CNS mechanisms responsible for respiratory homeostasis and for understanding pathologies where ventilatory failure results from dysfunction of CNS mechanisms controlling breathing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL002204-02
Application #
3074362
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Johnson, S M; Smith, J C; Feldman, J L (1996) Modulation of respiratory rhythm in vitro: role of Gi/o protein-mediated mechanisms. J Appl Physiol 80:2120-33
Johnson, S M; Smith, J C; Funk, G D et al. (1994) Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. J Neurophysiol 72:2598-608
Funk, G D; Smith, J C; Feldman, J L (1993) Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids. J Neurophysiol 70:1497-515
Greer, J J; Smith, J C; Feldman, J L (1992) Glutamate release and presynaptic action of AP4 during inspiratory drive to phrenic motoneurons. Brain Res 576:355-7
Smith, J C; Ballanyi, K; Richter, D W (1992) Whole-cell patch-clamp recordings from respiratory neurons in neonatal rat brainstem in vitro. Neurosci Lett 134:153-6
Greer, J J; Smith, J C; Feldman, J L (1992) Respiratory and locomotor patterns generated in the fetal rat brain stem-spinal cord in vitro. J Neurophysiol 67:996-9
Smith, J C; Ellenberger, H H; Ballanyi, K et al. (1991) Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254:726-9
Greer, J J; Smith, J C; Feldman, J L (1991) Role of excitatory amino acids in the generation and transmission of respiratory drive in neonatal rat. J Physiol 437:727-49
Smith, J C; Greer, J J; Liu, G S et al. (1990) Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity. J Neurophysiol 64:1149-69
Liu, G; Feldman, J L; Smith, J C (1990) Excitatory amino acid-mediated transmission of inspiratory drive to phrenic motoneurons. J Neurophysiol 64:423-36

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